Michal Schnaider Beeri is a psychologist with research experience in geriatrics and neuropsychology. Her long-term goal is to identify modifiable risk and protective factors for Alzheimer's disease (AD) and cognitive decline. Several risk factors for cardiovascular disease and diabetes in particular, have also been associated with risk for the occurrence of AD. Advanced Glycation End (AGE) products have been proposed as an explanation for the association between diabetes and AD and are the focus of the research project proposed in this application. This award will provide time and resources for Dr. Beeri to prepare for a career as an independent scientist, by acquiring knowledge and expertise in the following eight areas: 1) Epidemiology of AD, 2) Longitudinal statistical techniques, 3) Physiology of cardiovascular risk factors, 4) Epidemiology of cardiovascular risk factors, 5) AGEs, 6) The oldest old, 7) Differential diagnosis, and 8) Treatments for diabetes and AGEs. The Mount Sinai School of Medicine is an ideal environment for this training experience. The Psychiatry Department conducts extensive longitudinal research on AD, including risk factors research led by Dr. Jeremy Silverman, the principal mentor of this application. The Division of Diabetes and Aging of the Department of Medicine, directed by Dr. Helen Vlassara, a co-mentor, has pioneered AGE research in diabetes and will provide the infrastructure for large scale AGE studies. The objective of this project is to examine the role of AGEs in cognitive decline and AD incidence in 500 subjects participating in an ongoing longitudinal cardiovascular risk factors study for AD in the very old. Subjects' serum and urine AGEs (methylglycoxal, N-carboxymethyllysine (CML), and low molecule weight CML) and dietary AGEs will be assessed on a semi annual basis for up to 4 years, complementing their comprehensive cognitive and cardiovascular assessment. Identification of AGEs as a modifiable risk factor may lead to real public health gains among the elderly, by delaying or decreasing incidence of AD and cognitive decline.